Halofuginone (1) is a halogenated derivative of febrifugine (3), a natural product extracted from the roots of the hydrangea Dichroa febrifuga. Dichroa febrifuga is one of the “fifty fundamental herbs” of traditional Chinese medicine, originally used as an anti-malarial remedy (Jiang et al., Antimicrob. Agents Chemother. (2005) 49:1169-1176). Halofuginone, otherwise known as 7-bromo-6-chloro-3-[3-(3-hydroxy-2-piperidinyl)-2-oxopropyl]-4(3H)-quinazolinone, and halofuginone derivatives were first described in U.S. Pat. No. 2,694,711, incorporated herein by reference. Febrifugine has been shown to be the active ingredient in Dichroa febrifuga extracts; halofuginone was originally synthesized in search of less toxic anti-malarial derivatives of febrifugine. In addition to its anti-malarial properties, however, halofuginone has striking anti-fibrotic properties in vivo (Pines, et al., Biol. Blood Marrow Transplant (2003) 9: 417-425; U.S. Pat. No. 6,028,075, incorporated herein by reference). Halofuginone shows some toxicity in humans, such as nausea, vomiting, and fatigue, and possibly bleeding complications (de Jonge et al., Eur. J. Cancer (2006) 42: 1768-1774).

Since halofuginone has shown promising biological activities, there remains a need for identifying further related compounds with useful biological activities, especially those that may be less toxic than halofuginone or febrifugine.